Fibroblasts From the Oral Masticatory and Lining Mucosa Have Different Proliferation Rate and Gene Expression Profile

The connective tissue of lining and masticatory oral mucosae differ in the modulation of keratinization of overlying epithelium but also in immune responsiveness and proneness to drug-induced overgrowth, suggesting that fibroblasts from these two sites might differ in some intrinsic properties. Therefore, the present study compared the gene expression profiles and proliferation rates of these cells.

Primary human fibroblasts were retrieved from the masticatory hard palate (MFs) and the lining alveolar mucosa (LFs) of five individuals. RNA was isolated, followed by preparation of cDNA libraries and total RNA sequencing. The proliferation rate was determined colorimetrically.

Substantial differences were observed between MFs and LFs in specific gene groups and pathways. Significantly enriched gene ontology processes were focused on the extracellular components, including: “anatomical structure morphogenesis”, “cell adhesion” and “extracellular matrix structural constituent conferring tensile strength”. LFs exhibited significantly higher expression of the principal structural collagens and enzymes involved in collagen synthesis and degradation, suggesting a higher turnover rate of extracellular matrix components when compared to MFs. LFs also exhibited a higher expression of cranial neural crest markers and homeobox genes associated with positional memory, while MFs showed greater expression of molecules related to TGF-β signaling, which may be associated with fibrosis. In addition, MFs expressed higher levels of the EP₂ PGE₂ receptor and Toll-like receptor 1, pointing to different inflammatory and immunomodulatory properties of these cells. Finally, MFs exhibited a 10-30% higher proliferation rate.

Human MFs and LFs are phenotypically heterogeneous, presenting distinct gene expression profiles and different proliferation rates. These features may contribute to their specific physiological function and have relevance for potential therapeutic applications in the future. Our results suggest that due to their higher proliferative potential and cell plasticity, MFs may be more attractive for cell therapy and tissue engineering than LFs.